Summary of Clinical Trial Results For Laypersons

A study to learn how to best manage eye side effects in patients treated with depatuxizumab mafodotin for glioblastoma

Overall Summary

• Glioblastoma is the most common and • The study doctors checked patients’ visual deadliest type of brain cancer. acuity (sharpness of vision) throughout the study to find out which eye treatment • Treatment options are limited, and long-term reduced vision side effects. treatments are not available. • Around 50% of patients in the study had side • In this study, patients were treated with effects. The most common side effects were radiation therapy + depatuxizumab fatigue (tiredness), thrombocytopenia (low mafodotin (Depatux-M) + temozolomide level of platelets in the blood), increased (TMZ) followed by Depatux-M + TMZ. alanine aminotransferase in the blood • Patients treated with Depatux-M and other (may indicate liver damage), and increased similar drugs can have problems with their aspartate aminotransferase in the blood eyes (ocular side effects) that can be severe. (may indicate liver disease), • The study took place from July 2018 until • Depatux-M is no longer being developed for March 2020 in 4 countries. use at this time. • The main aim of the study was to find out if • If you participated in this study and have different eye treatments could reduce the questions about your individual care, contact ocular side effects in adult patients treated the doctor or staff at your study site. with Depatux-M for their glioblastoma. 1. General information about the study

1.1. What was the main objective of this study?

Glioblastoma is a high-grade glioma (brain tumor) and is the most common and deadliest form of brain cancer. It can occur in the brain or spinal column. Glioblastomas are very aggressive, because the tumor cells multiply quickly and tap into a large network of blood vessels. The exact cause of glioblastoma is unknown. Symptoms vary from patient to patient, but can include drowsiness, headache, memory and behavioral changes, vision changes, weakness or paralysis (loss of ability to move or feel) on one side of the body, and difficulty with speech. Standard treatment is surgical removal of the tumor followed by chemotherapy combined with radiation, but the chance of survival with or without treatment is low. For this reason, researchers are looking for new medicines like depatuxizumab mafodotin (Depatux-M) to treat patients with glioblastoma. Depatux-M is a type of drug called an antibody- drug conjugate (ADC) which means that it works to target and kill tumor cells while keeping healthy cells. Treatment with ADC drugs like Depatux-M can cause vision problems (ocular side effects) such as blurry vision, dry eyes, and other issues. Researchers planned this Phase 3 study of Depatux-M for adult patients with glioblastoma. Phase 3 studies test potential new treatments in a large number of patients with a condition or disease. In this study, doctors looked at the benefits of different types of eye treatments to reduce ocular side effects while patients received treatment for glioblastoma. This study was “open-label”, which means that both patients and study doctors knew which medicines were given to patients and what types of eye treatments were being used.

2 1.2. When and where was the study done? This study took place from July 2019 to March 2020 in the following countries: Australia, Germany, United Kingdom, and the United States.

2. What patients were included in this study? A total of 38 adult patients took part in the study. All patients had newly diagnosed glioblastoma and had tumor samples that showed a positive epidermal growth factor receptor (EGFR). EGFR is a receptor in the cell which if positive (or amplified) can cause rapid cell growth. 21% Women There were more men (79%) than women (21%) in the study 79% with an age range of 28 to 69 years of age. Men

3 3. Which medicines were studied? The medicine in this study was called depatuxizumab mafodotin (Depatux-M). All study patients received glioblastoma treatment with radiation therapy + Depatux-M + temozolomide (TMZ) followed by Depatux-M + TMZ. The patients were randomly placed into 3 different eye treatment groups by a computer program. This process is called “randomization” which helps make the groups similar and reduces differences between treatment groups. The different eye treatments included: • Standard steroids (eye drops used to treat inflammation in the eye) • Enhanced steroids (eye drops used to treat inflammation in the eye given at the maximum number of times per day and in an ointment form overnight) • Vasoconstrictors (eye drops that helps reduce swelling of blood vessels in the eye) • Cold compress (to help reduce swelling) The diagram below shows how the study was organized.

Glioblastoma treatment

Radiation Therapy + Depatux-M + TMZ ~ 4 weeks Depatux-M + TMZ (6 weeks) between (Up to 48 weeks)

Eye treatment

Standard Steroids

Standard Steroids + Vasoconstrictor + Cold Compress Patients randomized

Enhanced Steroids + Vasoconstrictor + Cold Compress

4 4. What were the side effects? Side effects are unwanted medical events that were considered by the study doctor to be at least possibly related to Depatux-M. A side effect is serious if it leads to death, is life-threatening, puts a patient in the hospital, keeps a patient in the hospital for a long time, or causes a disability that lasts a long time. About 7.9% of patients (3 patients) had serious side effects during the study. No patient stopped taking the study drug because of side effects during the study. No patient died during the study due to side effects or serious side effects. One additional patient had a serious side effect of ulcerative keratitis (open sore on the cornea) and eye infection. These side effects were considered possibly related to the steroids and use of a bandage contact lens (a contact lens used to protect an injured eye from rubbing of the eyelid). The table below shows information about the serious side effects patients had in the study that were considered at least possibly related to Depatux-M.

Standard steroids Standard steroids Enhanced steroids (14 Patients) + vasoconstrictor + vasoconstrictor + cold compress + cold compress (12 Patients) (12 Patients) Number of patients with serious 1 (7.1% of patients) 1 (8.3% of patients) 1 (8.3% of patients) side effects • Increased alanine aminotransferase 1 (7.1%) 0 (0.0%) 0 (0.0%) in blood (may indicate liver damage) • Thrombocytopenia (low level of 0 (0.0%) 1 (8.3%) 1 (8.3%) platelets in the blood)

5 About 50.0% of patients (19 patients) had side effects during the study. The table below shows information about the common side effects (in at least 2 or more patients in any group) in this study. The most common side effects were fatigue (tiredness), and increased alanine aminotransferase in blood (may indicate liver damage).

Standard steroids Standard steroids Enhanced steroids (14 Patients) + vasoconstrictor + vasoconstrictor + cold compress + cold compress (12 Patients) (12 Patients) Number of patients with at least 6 (42.9% of patients) 5 (41.7% of patients) 8 (66.7% of patients) one side effect Common Side Effects Side effects occurring in at least Fatigue (tiredness), Fatigue (tiredness), Fatigue (tiredness), 2 patients in any group increased alanine increased alanine increased alanine aminotransferase in aminotransferase in aminotransferase in blood (may indicate blood (may indicate blood (may indicate liver damage) liver damage), liver damage), increased aspartate thrombocytopenia aminotransferase (low level of platelets (may indicate in the blood) liver disease), thrombocytopenia (low level of platelets in the blood)

5. What were the overall results of the study? The study ended early because treatment with Depatux-M did not extend the length of survival of patients in another study of the drug. However, patients in this study were allowed to continue treatment with Depatux-M if their doctor thought it was in their best interest. Because the study was stopped early, study doctors were not able to learn which eye treatments helped with eye issues during treatment with Depatux-M.

6. How has the study helped patients and researchers? Given that treatment options for glioblastoma are limited, further research to new treatments may be considered. It is unknown whether further research into eye treatments will be considered. This summary only shows the results from this study, which may be different from the results of other studies.

6 7. Are there any plans for future studies? There are currently no plans for additional studies of Depatux-M.

8. Who sponsored this study? This study was sponsored by AbbVie. This summary was reviewed for readability by a patient advocacy group.

9. Where can I find out more information about this study?

Title of Study Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)

Protocol Number M16-534

Clinicaltrials.gov NCT03419403 https://clinicaltrials.gov/ct2/show/NCT03419403?term=NCT03419403&draw =2&rank=1

EudraCT 2017-003171-64 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-003171-64

Study Sponsor AbbVie, Inc. Phone: +1 800-633-9110 Email: [email protected]

Thank You

AbbVie wants to thank all the participants for their time and effort that went into making this study possible. Clinical study participants help advance science!

02-04-2021. This document includes known facts as of the time the document was finalized. 7